We have conducted a case-control study of ALS to investigate the role of cumulative lifetime exposure to lead and other neurotoxins, including mercury, solvents, and pesticides. Field work is complete; 110 clinic-based ALS cases, 31 clinic controls, and 270 populations controls were enrolled. We assessed lead exposure in three ways: we measured bone lead using x-ray fluorescence; we measured blood lead; and we administered a structure in-person interview to gather information on potential occupation, residential and lifestyle sources of exposure. ALS was associated with both blood and bone lead and with occupational exposure to lead, but not with residential or lifestyle exposures. We also found that ALS was associated with cigarette smoking but not with alcohol use. ALS was related to dietary lycopene but not to other antioxidant micronutrients or other components of diet.